Variant 2-47466567-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000251.3(MSH2):c.1511-91G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,235,160 control chromosomes in the GnomAD database, including 65,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.40 ( 14050 hom., cov: 33)

Exomes 𝑓: 0.30 ( 51797 hom. )

Consequence

MSH2
NM_000251.3 intron

Scores

Clinical Significance

Benign reviewed by expert panel B:4

Conservation

PhyloP100: -1.71

Variant links:

Genes affected

MSH2 (HGNC:7325): (mutS homolog 2) This locus is frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was discovered to be a human homolog of the E. coli mismatch repair gene mutS, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

MSH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 2-47466567-G-T is Benign according to our data. Variant chr2-47466567-G-T is described in ClinVar as [Benign]. Clinvar id is 90689.Status of the report is reviewed_by_expert_panel, 3 stars. Variant chr2-47466567-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSH2	NM_000251.3 linkuse as main transcript	c.1511-91G>T		intron_variant		ENST00000233146.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSH2	ENST00000233146.7 linkuse as main transcript	c.1511-91G>T		intron_variant		1	NM_000251.3	P1	P43246-1

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60638

AN:

151942

Hom.:

14031

Cov.:

show subpopulations

Gnomad AFR

AF:

0.623

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.340

Gnomad ASJ

AF:

0.227

Gnomad EAS

AF:

0.638

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.389

Gnomad MID

AF:

0.221

Gnomad NFE

AF:

0.277

Gnomad OTH

AF:

0.360

GnomAD4 exome

AF:

0.296

AC:

320283

AN:

1083098

Hom.:

51797

AF XY:

0.295

AC XY:

163294

AN XY:

553690

show subpopulations

Gnomad4 AFR exome

AF:

0.624

Gnomad4 AMR exome

AF:

0.297

Gnomad4 ASJ exome

AF:

0.234

Gnomad4 EAS exome

AF:

0.594

Gnomad4 SAS exome

AF:

0.319

Gnomad4 FIN exome

AF:

0.387

Gnomad4 NFE exome

AF:

0.264

Gnomad4 OTH exome

AF:

0.326

GnomAD4 genome

AF:

0.399

AC:

60707

AN:

152062

Hom.:

14050

Cov.:

AF XY:

0.402

AC XY:

29884

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.623

Gnomad4 AMR

AF:

0.340

Gnomad4 ASJ

AF:

0.227

Gnomad4 EAS

AF:

0.636

Gnomad4 SAS

AF:

0.341

Gnomad4 FIN

AF:

0.389

Gnomad4 NFE

AF:

0.277

Gnomad4 OTH

AF:

0.359

Alfa

AF:

0.267

Hom.:

1397

Bravo

AF:

0.404

Asia WGS

AF:

0.493

AC:

1714

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, no assertion criteria provided

research

Mayo Clinic Laboratories, Mayo Clinic

- -

Lynch syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Lynch syndrome

Benign:1

Benign, reviewed by expert panel

research

International Society for Gastrointestinal Hereditary Tumours (InSiGHT)

Sep 05, 2013

MAF >1% -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.037

DANN

Benign

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over